multiple ascending dose study of mhs552 in adults with type 1 diabetes mellitus

Conditions: Type 1 Diabetes Mellitus

Summary: the purpose of this two-part multiple ascending dose study is to evaluate the safety and tolerability of multiple doses of mhs552 in adults with type 1 diabetes mellitus. participants will be treated for 4 or 12 weeks followed by an 8 week follow-up period

this is a phase 1b, randomized, investigator and participant blinded, placebo controlled, multiple ascending dose (mad) study in adults with type 1 diabetes mellitus (adults aged 18-45 years, inclusive, diagnosed with t1dm within 5 years at the time of screening). this mad study will be conducted in two sequential parts, part a and part b. in part a, after an screening period of up to 28 days, participants will be randomized (in a 3:1 ratio) to mhs552 or placebo administered subcutaneously (s.c.) weekly for four weeks of treatment. part a will consist of up to 3 cohorts (low, medium, high dose), with approximately 4-8 participants completing each cohort (total of approximately 16 participants). participants will be followed-up during 8 weeks post last dose. the total duration of study participation of part a is approximately 106 days. in part b, after a screening period of up to 28 days, approximately 12 participants will be randomized (in a 2:1 ratio) to mhs552 or placebo administered s.c. weekly for 12 weeks of treatment (dose level 4). participants will be followed-up during 8 weeks post last dose with end of study (eos) visit at day 134. the total duration of study participation of part b is approximately 162 days.

Eligibility criteria:
inclusion criteria: * adult men and women ages 18 to 45, inclusive, body weight between ≥40 to ≤150 kg, inclusive, with t1dm, a maximum of 5 years from t1dm diagnosis at screening. * evidence of one or more t1dm autoantibody(ies) including glutamic acid decarboxylase (anti gad), protein tyrosine, phosphatase-like protein (anti-ia-2); zinc transporter 8 (anti-znt8); islet cell (cytoplasmic) (anti-ica) * residual pancreatic β-cell function (fasting c-peptide \>100 pmol/l \[0.30 ng/ml\] or random c peptide \>200 pmol/l \[0.60 ng/ml\]) exclusion criteria: * history of hypersensitivity to drugs of similar biological class, il-2 protein analogues, or immunoglobulin (igg1) proteins, hypersensitivity to any components of the study drug, or history of severe hypersensitivity reaction or anaphylaxis to biological agents, e.g. human monoclonal antibody. * use of other investigational drugs or use of immunosuppressive agents at the time of enrollment, or within 5 half-lives of enrollment, or until the expected pd effect has returned to baseline, whichever is longer; or longer if required by local regulations. * diabetes forms other than autoimmune type 1 such as maturity-onset diabetes of the young (mody), latent autoimmune diabetes of the adult (lada), acquired diabetes (secondary to medications or surgery), type 2 diabetes by judgement of the investigator. * diabetic ketoacidosis within 2 weeks. * polyglandular auto-immune disease, including but not limited to: addison's disease, pernicious anemia, celiac sprue and psoriasis. treated, stable hashimoto's thyroiditis is not exclusionary. * history of capillary leak syndrome (cls). * ongoing, and up to 2 weeks prior to screening, initiation of medications or change in dose of medications that may affect glucose control (e.g, systemic steroids, thiazides, beta blockers). other protocol-defined inclusion/exclusion criteria may apply

Keywords: type 1 diabetes mellitus, t1dm